DESCRIPTION: Hepatitis B virus (HBV) and hepatitis D virus (HDV) are important causes of acute and chronic hepatitis in humans. Although much is known about the replication of these viruses, less is known about how replication causes disease. Evidence suggests that, in HBV infection, host immune responses trigger liver injury and affect viral replication. This application proposes studies to further examine the nature of these immune responses and to determine if similar responses can occur in HDV infection; the ability of such responses to affect HDV RNA replication will also be examined. In addition, detailed studies of the mechanisms of HDV RNA replication will be conducted, with emphasis on the involvement of host factors in this important reaction.